title: Therapeutic implications of mesenchymal stem cells transfected with hepatocyte growth factor transplanted in rat kidney with unilateral ureteral obstruction.
abstract: OBJECTIVE
  The purpose of the study was to establish whether bone marrow mesenchymal stem cells (MSCs) transfected with hepatocyte growth factor (HGF) can migrate and localize in the rat's kidney with unilateral ureteral obstruction (UUO) and contribute to repair of renal fibrosis.
  
  
  METHODS
  We separated and cultured bone marrow-derived MSCs of male rats in vitro and transfected them with adenovirus-mediated HGF (Ad-HGF). The expression of HGF was measured with enzyme-linked immunosorbent assay. Sixty female rats were sham operated (n = 24) or subjected to left UUO: Ad-HGF-transfected MSCs, uninfected MSCs, or saline was injected into the rat's tail vein. Kidney tissue was collected at the end of the seventh or 14th day after operation. The distribution of Y chromosome in the kidney after Ad-HGF-transfected MSCs transplantation was determined by an in situ hybridization method. As the hallmark of myofibroblasts, α-smooth muscle actin (expression of which significantly increases in the presence of renal fibrosis) was detected by immunohistochemistry in all UUO rats' left kidney tissue.
  
  
  RESULTS
  Y chromosome-positive cells were found only in the obstructed kidney of the transplantation group. The positive cells were mainly distributed in the tubular cells. The average intensity of immunolabeling for α-smooth muscle actin in the transplanted group significantly decreased compared with sham-transplanted group (P < .05), and the expression in the rats injected with uninfected MSCs was higher than that in the rats with MSCs transfected with HGF (P < .05).
  
  
  CONCLUSIONS
  Mesenchymal stem cells transfected with HGF can migrate to the rat kidney with UUO and are mainly distributed in the region of renal tubular epithelial cells. The data indicate that MSCs transfected with HGF contribute to a reduction of renal fibrosis after ureteral obstruction and suggest that this may be exploited therapeutically.
authors.affiliation: Department of Pediatric Surgery, ShengJing Hospital of China Medical University, Shenyang, PR China. liuxinlobo@hotmail.com
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Ge
authors.initials: G
authors.lastname: Liu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006869:Hydronephrosis / Q000209:etiology / Q000473:pathology; D007668:Kidney; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D014161:Transduction, Genetic; D014517:Ureteral Obstruction / Q000601:surgery*
chemical_list: C066855:HGF protein, human; D011993:Recombinant Fusion Proteins; D017228:Hepatocyte Growth Factor